Decreased IFN-γ production in infants with acute RSV infection related to lower TLR8 expression in NK cells

Toll-like receptors (TLRs), as a part of the innate immunity, provide first line of defense able to activate immune system upon pathogen challenge. Respiratory syncytial virus (RSV) is single-stranded RNA virus which can cause severe lower respiratory tract infection (LRTI) in infants. TLR8 recognizes single-stranded viral RNA and initiates cascade of antiviral mechanisms necessary to limit virus spread and development of specific immune reaction. NK cells are among early responder cells in viral infections with ability to directly recognize and kill infected cells. Although NK cytolytic activity is mediated via killer activating receptors and FcγR’s it could be significantly up-regulated by IFN type I and II cytokines, in paracrine and autocrine fashion. Since peripheral blood NK cells express TLR8, we postulate that lower TLR8 receptor expression could be related to inability of NK cells to control RSV replication, to induce IFN-γ production and to participate in development of effective specific anti-RSV immune response in infants with RSV infection. In our study specific monoclonal antibody raised against human TLR8 was used to determine expression in peripheral blood NK cells from RSV-infected infants during acute infection, healthy infants and adults. Functional status of TLR8 in monocytes was assessed in vitro by intracellular IFN-γ upon TLR8-specific stimulation. Infants in acute phase of RSV infection had lower percentages of TLR8- expressing NK cells than healthy infants and adults. Lower TLR8 levels (mean fluorescence intensity) in NK cells during acute RSV- infection were accompanied by lower TLR8- mediaded IFN-γ production. Moreover, NK cell percentages and expression levels of TLR8 negatively correlated with severity of infection, assessed as hospitalization duration. In conclusion, lower expression of TLR8 in NK cells from RSV-infected infants could imply inadequate engagement of antiviral innate immune mechanisms responsible for RSV replication control and generation of effective immune response that might lead to exaggerated inflammation frequently observed in infants.